Abstract In platelets, phosphatidylserine (PS) is present exclusively in the inner leaflet of the membrane bilayer. Upon activation with some agonists, platelets externalize PS and provide a procoagulant surface. Exposure of PS is accompanied by the release of PS-rich procoagulant membrane fragments called platelet-derived microvesicles. Deficiency of PS exposure and microvesiculation leads to an inherited bleeding disorder, Scott syndrome. Increased microvesicles have been detected in conditions associated with either arterial or venous thrombosis. These associations suggest that, while they may be necessary for normal hemostasis, elevated microvesicles predispose to thrombosis. We have identified lactadherin and Del-1 (developmentally expressed locus-1) as mediators of microvesicles clearance. Lactadherin and Del-1 are present in circulating microvesicles and promotes their phagocytosis by macrophages in a concentration-dependent manner in vitro. Lactadherin-deficient mice have increased microvesicles in the circulation and an enhanced thrombin generation in their plasma. Furthermore, in a light-dye-induced endothelial cell injury/thrombosis model, lactadherin-deficient mice have increased thrombotic tendency compared to wild type littermate controls. Our goals in the current proposal are to define the mechanism(s) of microvesicles clearance and its relation to thrombosis. We will also test the hypothesis that impaired clearance of the microvesicles per sh leads to a hypercoagulable state in antiphospholipid antibody syndrome. The specific aims of this proposal are to further characterize the role of lactadherin and Del-1 in the clearance of microvesicles in vivo and to test the hypothesis that microvesicles causes thrombosis in antiphospholipid syndrome.